Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune response, and tissue damage associated with COVID-19 demise are poorly described and understood due to safety concerns. Using post-mortem lung tissues from uninfected and COVID-19 deadly cases as well as an unbiased combined analysis of histology, multi-viral and host markers staining, correlative microscopy, confocal, and image analysis, we identified three distinct phenotypes of COVID-19-induced lung damage. First, a COVID-19-induced hemorrhage characterized by minimal immune infiltration and large thrombus; Second, a COVID-19-induced immune infiltration with excessive immune cell infiltration but no hemorrhagic events. The third phenotype correspond to the combination of the two previous ones. We observed the loss of alveolar wall integrity, detachment of lung tissue pieces, fibroblast proliferation, and extensive fibrosis in all three phenotypes. Although lung tissues studied were from lethal COVID-19, a strong immune response was observed in all cases analyzed with significant B cell and poor T cell infiltrations, suggesting an exhausted or compromised immune cellular response in these patients. Overall, our data show that SARS-CoV-2-induced lung damage is highly heterogeneous. These individual differences need to be considered to understand the acute and long-term COVID-19 consequences.
【저자키워드】 COVID-19, lung, immune, immune activation, SARS – CoV – 2, 【초록키워드】 public health, SARS-CoV-2, Cytokine storm, coronavirus, immune response, fibrosis, immune infiltration, virus, Immune cell infiltration, B cell, Consequences, T cell, Microscopy, phenotype, histology, disease, patients, cellular response, Lung pathology, marker, Combination, Analysis, hemorrhage, lung damage, proliferation, Phenotypes, acute respiratory syndrome, tissue, tissue damage, lung tissue, heterogeneous, demise, staining, second, strong immune response, alveolar, fibroblast, Host, uninfected, described, analyzed, characterized, hemorrhagic events, post-mortem lung, with COVID-19, 【제목키워드】 SARS-CoV-2,